Ionizing radiation promotes lung injury by inducing ferroptosis-driven senescence in epithelial cells via NCOA4-mediated ferritinophagy - PubMed
6 hours ago
- #Senescence
- #Lung Injury
- #Ferroptosis
- Ionizing radiation (IR) induces lung injury by promoting ferroptosis-driven senescence in lung epithelial cells via NCOA4-mediated ferritinophagy.
- Radiation-induced lung injury (RILI) is a dose-limiting factor in thoracic radiotherapy, with no effective treatments currently available.
- IR causes mitochondrial dysfunction and senescence in lung epithelial cells, leading to the release of senescence-associated secretory phenotype (SASP).
- Ferroptosis inhibitor Ferrostatin-1 (Fer-1) effectively inhibits IR-induced mitochondrial dysfunction and senescence.
- IR-induced iron overload and ferroptosis are linked to ferritin degradation, which can be mitigated by autophagy inhibitor 3-methyladenine (3-MA).
- NCOA4 knockdown in vitro reduces iron overload, ferroptosis, and cellular senescence in lung epithelial cells.
- In vivo, compound 9a disrupts NCOA4-FTH interaction, inhibiting ferritinophagy, reducing iron levels and ferroptosis, and improving mitochondrial function and epithelial cell senescence.
- The study highlights ferroptosis as a key regulator of IR-induced senescence and NCOA4-mediated ferritinophagy as critical in RILI pathogenesis.